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Background and Objective <p>Phytocannabinoids, the main bioactive compounds of <i>Cannabis sativa</i>, are metabolized by hepatic cytochrome P450 (CYP450) enzymes and can also modulate their function. Since CYP450 isoforms are responsible for the metabolism of approximately 80% of therapeutic drugs, interactions between phytocannabinoids and these enzymes may have clinically relevant consequences. The objective of this systematic review was to systematically evaluate the effects of phytocannabinoids on the activity and expression of hepatic CYP450 complex enzymes.</p> Methods <p>This systematic review was conducted according to PRISMA guidelines. Literature searches were performed in PubMed, SciELO, ScienceDirect, and Scopus, covering studies published between January 2019 and March 2025. In vitro, in vivo, or ex vivo studies that evaluated the modulatory effects of phytocannabinoids on hepatic CYP450 isoforms were included. After applying the inclusion and exclusion criteria, four studies met the eligibility requirements.</p> Results <p>The selected studies reported that phytocannabinoids, particularly cannabidiol (CBD), exert inhibitory effects on several CYP450 isoforms, including CYP3A4, CYP2C9, and CYP2C19. One study indicated that CYP2C19 activity could also be induced under certain conditions. In contrast, CYP2D6 showed minimal or no modulation. Overall, CBD was consistently identified as a potent inhibitor of CYP enzymes responsible for drug metabolism.</p> Conclusion <p>Phytocannabinoids, particularly CBD, influence the activity of key CYP450 system enzymes, predominantly through inhibition. These findings highlight the potential for drug–cannabinoid interactions and emphasize the need for additional clinical and mechanistic studies to assess safety and pharmacokinetic implications in patients using cannabis-based therapies.</p> Graphical Abstract <p></p>

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The Influence of CBD and THC on Hepatic Enzymes of the Human Cytochrome P450 Complex Family: A Systematic Literature Review

  • 期刊论文

  • 发表日期：

    2025年12月19日

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  • Mariana Candeias dos Santos,
  • Anderson Matheus Pereira da Silva,
  • Maria da Vitória Santos do Nascimento,
  • Tânia Maria Sarmento da Silva,
  • Eryvelton de Souza Franco,
  • Maria Bernadete de Sousa Maia

摘要

Background and Objective

Phytocannabinoids, the main bioactive compounds of Cannabis sativa, are metabolized by hepatic cytochrome P450 (CYP450) enzymes and can also modulate their function. Since CYP450 isoforms are responsible for the metabolism of approximately 80% of therapeutic drugs, interactions between phytocannabinoids and these enzymes may have clinically relevant consequences. The objective of this systematic review was to systematically evaluate the effects of phytocannabinoids on the activity and expression of hepatic CYP450 complex enzymes.

Methods

This systematic review was conducted according to PRISMA guidelines. Literature searches were performed in PubMed, SciELO, ScienceDirect, and Scopus, covering studies published between January 2019 and March 2025. In vitro, in vivo, or ex vivo studies that evaluated the modulatory effects of phytocannabinoids on hepatic CYP450 isoforms were included. After applying the inclusion and exclusion criteria, four studies met the eligibility requirements.

Results

The selected studies reported that phytocannabinoids, particularly cannabidiol (CBD), exert inhibitory effects on several CYP450 isoforms, including CYP3A4, CYP2C9, and CYP2C19. One study indicated that CYP2C19 activity could also be induced under certain conditions. In contrast, CYP2D6 showed minimal or no modulation. Overall, CBD was consistently identified as a potent inhibitor of CYP enzymes responsible for drug metabolism.

Conclusion

Phytocannabinoids, particularly CBD, influence the activity of key CYP450 system enzymes, predominantly through inhibition. These findings highlight the potential for drug–cannabinoid interactions and emphasize the need for additional clinical and mechanistic studies to assess safety and pharmacokinetic implications in patients using cannabis-based therapies.

Graphical Abstract